We have previously measured hepatic prolyl hydroxylase (EC 1.14.11.2; Proline, 2-oxyglutarate Dioxygenase) in 134 patients with alcoholic liver disease to determine the feasibility of using prolyl hydroxylase as a marker of hepatic fibrogenesis. Prolyl hydroxylase activity and the rate of in vitro collagen synthesis were significantly correlated (r equals 0.58) when these parameters could be measured in samples of the same liver biopsy. Mean prolyl hydroxylase activity was significantly elevated in all groups of alcoholic patients with alcoholic liver disease, and alcoholic patients with early cirrhosis had enzyme activity (mean plus or minus S.E.:1.494 plus or minus 0.192 m units/mg protein) significantly elevated over all other groups and 11-fold over non-alcoholic patients with normal liver biopsy tissue. However, no correlation was found between liver and serum enzyme levels in these patients. Liver contains large quantities of protein which is antigenecally related to prolyl hydroxylase (cross reacting protein or CRP) which can be detected only by cross reactivity of this material with antibody directed against human prolyl hydroxylase. Recently, this antibody has been raised against purified human umbilical cord. In this proposal we are requesting funds to assay serum and liver specimens from the patient population being followed for prolyl hydroxylase activity, for prolyl hydroxylase CRP in order to determine if a correlation exists between liver and serum CRP, or between CRP and hepatic histopathology. Such a correlation would suggest the usefullness of serum CRP levels as a non-invasive diagnostic parameter for detecting liver fibrogenesis.